JVI Accepts, published online ahead of print on 21 May 2008

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J. Virol. doi:10.1128/JVI.00800-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Transmission of HIV-1 from a Patient Who Developed AIDS to an Elite Suppressor

Justin R. Bailey, Karen O'Connell, Hung-Chih Yang, Yefei Han, Jie Xu, Benjamin Jilek, Thomas M. Williams, Stuart C. Ray, Robert F. Siliciano, and Joel N. Blankson^*

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore Maryland 21205; Department of Pathology, University of New Mexico School of Medicine and Tricore Reference Laboratories, Albuquerque, New Mexico 87131; and the Howard Hughes Medical Institute, Chevy Chase, Maryland

^* To whom correspondence should be addressed. Email: jblanks{at}jhmi.edu.

Elite suppressors (ES) are untreated HIV-1 infected patients who maintain viral loads of < 50 copies/ml. The mechanisms involved in this control of viral replication remain unclear. Prior studies have suggested that these patients, as well as long-term non-progressors (LTNP), are infected with defective HIV-1 variants. Other reports have shown that the HLA-B*27 and B*57 alleles are overrepresented in these patients, suggesting that host factors play a role in the control of viral replication. In order to distinguish between these hypotheses, we studied differences in viral isolates and immune responses of an HIV-1 transmission pair. While both patients are HLA-B*57 positive, the transmitter progressed to AIDS whereas the recipient, who is also HLA-B*27 positive, is an ES. Isolates from both patients were replication-competent and contained the T242N escape mutation in Gag which is known to decrease viral fitness. While the acquisition of compensatory mutations occurred in isolates from the progressor, a superior HIV-specific CD8⁺ T cell response in the ES appears to have prevented viral replication and thus the evolution towards a more fit variant. In addition, CD8⁺ T cells in the ES have selected for a rare mutation in an immunodominant HLA-B*27 restricted Gag epitope which also has a negative impact on fitness. The results strongly suggest that through direct and indirect mechanisms, CD8⁺ T cells in some ES control HIV-1 isolates that are capable of causing profound immunosuppression.

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